Collapsing glomerulopathy due to hemophagocytic lymphohistiocytosis: A case report

Introduction: Collapsing glomerulopathy (cFSGS) is most commonly seen in association with Human Immunodeficiency Virus infection (HIVAN) and can also occur in association with viral and non viral infections, autoimmune diseases, malignancy and drug exposure Patients typically present with rapidly worsening renal function and nephrotic syndrome We report a case of cFSGS due to Hemophagocytic lymphohistiocytosis (HLH) Case Description: A 41-year-old man with acute myeloid leukemia and allogenic hematopoetic stem cell transplant with graft versus host disease on Ruxolitinib, was admitted for hypervolemia, respiratory failure, rapidly rising creatinine and nephrotic range proteinuria He was noted to have anemia, thrombocytopenia, high LDH, low haptoglobin and abnormal liver function tests He underwent renal biopsy that showed collapse of capillary loops and podocyte hyperplasia on light microscopy with marked foot process effacement on electron microscopy Extensive work up was pursued to identify the etiology of cFSGS Infectious work up including HIV, hepatitis B and C, parvo virus B19, BK virus, CMV, EBV, HSV, Human herpes virus 6, SARS-COV-2, Mycobacteria, fungal, and parasitic organisms was negative He had marked elevation of ferritin at 35,000ng/ml and triglycerides at 1,529 mg/dL in the setting of severe pancytopenia and fever raising concern for HLH He underwent bone marrow biopsy that showed hemophagocytosis of nucleated cells supporting diagnosis of HLH Soluble interleukin 2 receptor levels (sCD25) were normal consistent with the use of Ruxolitinib Despite receiving Anakinra, Rituximab, and Dexamathasone for HLH he deteriorated clinically and was transitioned to comfort care Discussion: cFSGS has been associated lupus, IgA nephropathy, diabetic nephropathy, thrombotic microangiopathy/acute glomerular ischemia, bisphosphonate therapy, HLH, and infections like HIV, Parvo virus B19, pulmonary tuberculosis, CMV and more recently SARS-COV-2 Treatment of cFSGS is directed towards the underlying cause cFSGS complicating HLH is rare Excessive immune activation with release of pro inflammatory cytokines targeting the podocytes is hypothesized to cause cFSGS in HLH Renal prognosis appears to be poor despite therapy and most patients remain dialysis dependent HLH has been reported post stem cell transplant and should be considered in the differential diagnosis of cFSGS